1. Field of the Invention
The present invention is generally related to a glycine derivative, and more particularly to a glycine derivative capable of inhibiting melanin formation and composition using the same.
2. Description of the Prior Art
In general, melanin formation is considered to be related to tyrosinase. Tyrosine naturally exists in epidermal cells and is the precursor or melanin. Melanin formation comprises the following steps tyrosine→Dopa→Dopaquinone→Dopachrome→melanin, melanin is formed and tyrosinase is an important enzyme in the melanin formation process. The hydroxylase activity of tyrosinase catalyzes the reaction of converting tyrosine into dopa and the oxidase activity of tyrosinase catalyzes the reaction of converting dopa into dopaquinone. As long as a substance can effectively act on epidermal cells to inhibit melanogenesis or inhibit the formation of any product in the sequence of melanin formation, the substance can be used as an effective ingredient for skin whitening. The first step to initiate melanin formation is that tyrosinase catalyzes the reaction of converting tyrosine into dopa and thus the whole sequence of melanin formation can be inhibited by inhibiting the activity of tyrosinase. The tyrosinase inhibitor is one of the effective ingredients for skin whitening.
However, the mechanisms of inhibiting melanin formation of various effective skin whitening ingredients are not all the same and also are not completely realized. The well-known skin whitening ingredients, such as Kojic acid, ascorbic acid derivatives, arbutins, etc., are compounds capable of inhibiting the activity of tyrosinase.
Kojic acid is not stable in a solution to make formulation manufacturing process complicate (referring to U.S. Pat. No. 6,306,376) and may cause skin allergy (referring to Contact Dermatitis, January 1995, Vol. 42(1), Page 9˜13) while applied as a skin care product. The above mentioned problems both restrict the applicability of skin whitening formulation thereof.
Ascorbic acid is very unstable and can be easily oxidized and deteriorated. Thus, usually an ascorbic acid derivative is used instead to improve the stability of formulation. However, in the formulation, stabilizer like sodium hydrogen sulfite is added or a buffer solution is used to reduce the level of oxidation or color change (referring to embodiments of U.S. Pat. No. 6,801,050). However, using sulfite as a stabilizer causes the resulting product having an irritating smell problem (referring to U.S. Pat. No. 6,020,367). Therefore, such a method cannot solve both the color and smell problems in the whitening formulation.
Although arbutin has whitening effect, the structure of arbutin is glycosylated hydroquinone and the formulation containing arbutin may have color change due to oxidation of aromatic phenol moiety to cause the difficulty in formulation manufacturing. Besides, the water solubility of arbutin is low to result in low concentration in the formulation so that the resulting whitening effect is low in practice (referring to Japan patent application No. 2009-67691). Japan patent application No. 2009-67691 discloses whitening cosmetics containing nano arbutin but it has problems of being very difficult to produce, inconvenient in use, and difficulty in being absorbed by skin.
U.S. Pat. No. 6,365,135 discloses use of amino phenol amide derivatives as depigmentation agents. Besides, Japan patent application No. H07-061905 and H07-233022 also disclose amino phenol amide derivatives as whitening ingredients. In the reports, it is suggested that tyrosinase is copper-containing polyphenol oxidase and a compound containing phenol structure(s) may be an effective ingredient to inhibit the activity of tyrosinase because of the structural similarity with tyrosinase. However, the structure of amino phenol amide derivatives comprises aromatic phenol moieties and derivatives thereof that are easy to be oxidized.
Japan patent application No. H05-032533, H06-345797, and H05-170637 disclose various dipeptides having whitening effect. In these prior arts, the amino acid side chains in dipeptides all comprise thiol groups and derivatives thereof, aromatic groups or aromatic phenol groups and derivatives thereof. The melanin inhibition mechanisms of the disclosed dipeptides are not clear. For example, the tyrosinase inhibiting rates of dipeptides disclosed in table 1 of Japan patent application No. H05-170637 are in the range of 3%˜56%. Therefore, not all dipeptides are good whitening ingredients.
However, in practice, when manufacturing and applying the whitening skin care formulation, except the effectiveness of the major ingredients, the stability in the formulation should also be considered at the same time to avoid generating cross reaction with solvents and other additives in the formulation to cause formulation deterioration to generate color and smell problems. In view of the above problems, it is necessary to develop a novel whitening ingredient suitable for various whitening care products, such as cream, emulsion, gel, lotion, etc., and having stability in a formulation to fulfill the industrial needs.